MaxWell Monthly Must-Reads | World Organoid Research Day

Today is World Organoid Research Day! Let’s celebrate the incredible advances being made in this fascinating and yet rapidly evolving field of research by raising awareness on the potential of organoids in advancing biomedical research, drug discovery, regenerative medicine, modeling complex diseases, personalized medicine, reducing animal testing, and advancing stem cell research.

Grown from human stem cells, organoids are miniaturized three-dimensional structures that closely resemble the architecture and function of real human organs, providing a more complex and comprehensive model of human biology than traditional cell cultures or animal models. Recent advances in stem cell research have generated a wide range of organoids models, including but not limited to the brain, heart, liver, pancreas, muscle, retina, kidney, lung, and intestine.

With these self-organizing 3D cellular models, rapid, non-invasive, patient-tailored, and cost-effective drug screenings and disease modeling are now becoming a reality. Under this shared vision, there is an urge to assess the molecular composition, genetic expression, and physiological function of organoids, now more than ever!

Considering that some types of human organs consist of cells that uses electrical signals to communicate with one and another, including the brain, retina, muscle, heart, and intestine, the characterization of these properties is a critical consideration in the validation of their organoid models. To obtain these functional physiological readouts, electrophysiological tools such as calcium imaging, patch clamp as well as microelectrode array (MEA) recordings are sought after and proved their worth.

MEA technology enables easy capture of electrical activity in real-time and label-free across a spatially confined area, offering valuable insights into their functional phenotype. Beyond that, our High-Density MEA (HD-MEA) technology offers unparalleled spatial resolution and offers users a powerful, user-friendly, and non-invasive means to characterize organoids with electrical properties over extended periods of time. These advantages enable and promote organoids as the up-and-coming model for disease modeling and therapeutic development.

This month, in celebration of the World Organoid Research Day on March 22nd, we present you with a collection of publications on organoid research, some of which highlight the potential of our complimentary HD-MEA technology.

Review | Organoids
by Zixuan Zhao, Xinyi Chen, Anna M. Dowbaj, Aleksandra Sljukic, Kaitlin Bratlie, Luda Lin, Eliza Li Shan Fong, Gowri Manohari Balachander, Zhaowei Chen, Alice Soragni, Meritxell Huch, Yi Arial Zeng, Qun Wang and Hanry Yu, Nat Rev Methods Primers, December 2022
A thorough and recent review on organoids and their applications, ranging from furthering our understanding of development and regeneration, to guiding diagnostics, disease modeling, drug discovery, and personalized medicine. The review also discusses strategies undertaken to generate robust organoid models, as well as their limitations across different applications and the priorities for organoid engineering in the coming years.

Editorial | Organoids: Expanding Applications Enabled by Emerging Technologies
by ChangHui Pak, Yubing Sun, Journal of Molecular Biology, February 2022
The editorial article covers the development and advances in organoid systems, to  better mimic the physiological conditions of the tissue they represent, the disease they model and how emergent biotechnological tools are facilitating these investigations. Be sure to check out the interesting reviews that’s highlighted!  

Brain Organoids Publication | Network and Microcircuitry Development in Human Brain Organoids
by Francesca Puppo and Alysson Renato Muotri, Biological Psychiatry, August 2022
Transitioning from the traditional molecular approaches to characterize organoids to include functional physiological readouts is challenging, this commentary provides some sound insights.

Organoids Inteligence | Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish
by Lena Smirnova, Brian S. Caffo, David H. Gracias, Qi Huang, Itzy E. Morales Pantoja, Bohao Tang, Donald J. Zack, Cynthia A. Berlinicke, J. Lomax Boyd, Timothy D. Harris, Erik C. Johnson, Brett J. Kagan, Jeffrey Kahn, Alysson R. Muotri, Barton L. Paulhamus, Jens C. Schwamborn, Jesse Plotkin, Alexander S. Szalay, Joshua T. Vogelstein, Paul F. Worley and Thomas Hartung, Frontiers in Science, February 2023
This publication presents the potential for neural organoids to replicate aspects of learning, memory, and cognition in vitro, here coined  as “organoid intelligence” (OI). The authors discuss the feasibility and approaches to establish OI as a form of biocomputing as well as highlighting their applications for faster decision-making, continuous learning, and identifying novel therapeutic strategies for neurodegenerative diseases. Beyond the science and the engineering, the authors also discuss the underlying ethical implications that must not be overlooked.

Brain Organoids Publication & HD-MEA | Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A
by Jonas Van Lent, Leen Vendredy, Elias Adriaenssens, Tatiana Da Silva Authier, Bob Asselbergh, Marcus Kaji,  Sarah Weckhuysen, Ludo Van Den Bosch, Jonathan Baets and Vincent Timmerman, Brain, December 2022.
Many neural organoid models focus on the central nervous system (CNS), this publication presents a novel  organoid model that incorporate the myelinating human Schwann cells to mimic the peripheral nervous system (PNS) and exploiting it to study the disease signatures of Charcot-Marie-Tooth disease type 1A.

Brain Organoids Publication & HD-MEA | Generation of human striatal-midbrain assembloids from human pluripotent stem cells to model alpha-synuclein propagation
by Hoang-Dai Tran, Min-Kyoung Shin, Charlotte Denman, Run-Run Han, Bernd Kuhn, Gordon Arbuthnott and Junghyun Jo, Cell Stem Cell, December 2022
Let’s jump into the regionalized organoids. Researchers developed assembloids mimicking the basal ganglia by combining  striatal and midbrain organoids. That’s not all, they also showcased the ability of this system to model neurodegenerative disorders targeting the basal ganglia, namely Parkinson’s Disease, and screen promising therapeutic strategies.

Brain Organoids Publication & HD-MEA | Functional neuronal circuitry and oscillatory dynamics in human brain organoids
by Tal Sharf, Tjitse van der Molen, Stella M. K. Glasauer, Elmer Guzman, Alessio P. Buccino, Gabriel Luna, Zhuowei Cheng, Morgane Audouard, Kamalini G. Ranasinghe, Kiwamu Kudo, Srikantan S. Nagarajan, Kenneth R. Tovar, Linda R. Petzold, Andreas Hierlemann, Paul K. Hansma and Kenneth S. Kosik, Nature Communications, July 2022
Ever wondered how neurons within neural organoids are connected with each other? Check out how our HD-MEA technology is enabling the authors here to find an answer. They even took it a step further and investigated how diazepam, a commonly prescribed anxiety relieving drug impacts the overall and neuron-to-neuron functional connectivity.

Brain Organoids Publication & HD-MEA | Functional imaging of brain organoids using high-density microelectrode arrays
by Manuel Schröter, Congwei Wang, Marco Terrigno, Philipp Hornauer, Ziqiang Huang, Ravi Jagasia, and Andreas Hierlemann, MRS Bulletin, June 2022
Want to learn more about how to functionally characterize your organoids? Here’s how! Our users provide a comprehensive guide on how our HD-MEAs can be exploited to record and investigate neural organoids across multiple timepoints. They are just scratching the surface. Stay tuned for more!

Brain Organoids Publication & HD-MEA | Autism genes converge on asynchronous development of shared neuron classes
by Bruna Paulsen, Silvia Velasco, Amanda J. Kedaigle, Martina Pigoni, Giorgia Quadrato, Anthony J. Deo, Xian Adiconis, Ana Uzquiano, Rafaela Sartore, Sung Min Yang, Sean K. Simmons, Panagiotis Symvoulidis, Kwanho Kim, Kalliopi Tsafou, Archana Podury, Catherine Abbate, Ashley Tucewicz, Samantha N. Smith, Alexandre Albanese, Lindy Barrett, Neville E. Sanjana, Xi Shi, Kwanghun Chung, Kasper Lage, Edward S. Boyden, Aviv Regev, Joshua Z. Levin and Paola Arlotta, Nature, February 2022
Combining the traditional molecular work on neural organoids with the current genetic investigations and up-and-coming functional readouts, these authors undertook an ambitious plan to understand the intricacies underlying the shared abnormalities across autism-spectrum disorder risk genes.

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